The effects of amyloid-β on the activity and excitability of individual neurons in the early and advanced stages of the pathological progression of Alzheimer's disease remain unknown. We used invivo intracellular recordings to measure the ongoing and evoked activity of pyramidal neurons in the frontal cortex of APPswe/PS1dE9 transgenic mice and age-matched nontransgenic littermate controls. Evoked excitability was altered in both transgenic groups: neurons in young transgenic mice displayed hypoexcitability, whereas those in older transgenic mice displayed hyperexcitability, suggesting changes in intrinsic electrical properties of the neurons. However, the ongoing activity of neurons in both young and old transgenic groups showed signs of hyperexcitability in the depolarized state of the membrane potential. The membrane potential of neurons in old transgenic mice had an increased tendency to fail to transition to the depolarized state, and the depolarized states had shorter durations on average than did controls. This suggests a combination of both intrinsic electrical and synaptic dysfunctions as mechanisms for activity changes at later stages of the neuropathological progression.
|Number of pages||10|
|Journal||Neurobiology of Aging|
|State||Published - Sep 2014|
Bibliographical noteFunding Information:
The authors thank Professor Moshe Abeles, Professor Israel Nelken, and Professor Bradley T. Hyman for their valuable suggestions. Funding for this study was provided by the National Institute on Aging ( AG024238 ) and the Legacy Heritage Bio-Medical Program of the Israel Science Foundation ( 688/10 ).
- Alzheimer's disease
- Background activity
- Down state
- Membrane potential
- Mouse model
- Up state